Kynurenine/Tryptophan Ratio in Hypertension Associated to Obstructive Sleep Apnea

NCT ID: NCT04646902

Last Updated: 2023-12-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 203 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-03-25
• Study Completion Date: 2024-03-01

Brief Summary

Obstructive Sleep Apnea (OSA) is an independent risk factor for hypertension (HTN) and the most common cause of resistant HTN. The mechanisms underlying OSA-associated HTN are not completely understood. This is crucial to find novel therapeutic targets of OSA-associated HTN. The Aryl Hydrocarbon Receptor (AHR) is a cytosolic transcription factor that has been linked with the pathogenesis of HTN.

This study aims to evaluate the role of endogenous ligands of AHR such as kynurenine in discriminating patients with OSA-associated HTN. For that aim, a case-control study will be performed in patients with and without hypertension exposed and not exposed to OSA. Kynurenine and other metabolites will be quantified in urine and serum samples.

Conditions

Hypertension Secondary

Keywords

hypertension; obstructive sleep apnea; tryptophan; aryl hydrocarbon receptor

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

HTN_OSA

Patients with hypertension* with obstructive sleep apnea**

• Hypertension will be defined as: i) use of antihypertensive drug(s) and stable dose for at least 2 weeks prior to inclusion; or ii) in untreated patients: office systolic blood pressure values >= 140 mmHg and/ or diastolic blood pressure values >= 90 mmHg.

** OSA will be defined with a polysomnography level 1, 2 or 3 performed within the previous twelve months with:

• an apnea-hypopnea index > 5 events per hour (with more than 50% of obstructive events) associated with symptoms (associated sleepiness, fatigue, insomnia, snoring, subjective nocturnal respiratory disturbance or observed apnea) or medical/psychiatric disorder (hypertension, coronary artery disease, atrial fibrillation, congestive heart failure, stroke, diabetes, cognitive dysfunction, or mood disorder), OR
• an apnea-hypopnea index > 15 events per hour, AND
• no significant changes in health, medications, or lifestyle since the polysomnography.

No interventions assigned to this group

HTN_NoOSA

Patients with hypertension without obstructive sleep apnea

No interventions assigned to this group

NoHTN_OSA

Patients without hypertension with obstructive sleep apnea

No interventions assigned to this group

NoHTN_NoOSA

Patients without hypertension without obstructive sleep apnea (healthy controls)

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Adults ≥ 30 years old attending the outpatient clinics of the clinical sites.
• Diagnosis of hypertension defined either as: a) use of antihypertensive drug(s) and stable dose for at least 2 weeks prior to inclusion; or b) in untreated patients: office systolic blood pressure values >= 140 mmHg and/ or diastolic blood pressure values >= 90 mmHg.
• Able to understand and communicate effectively with study personnel.
• Giving written informed consent to participate.

Exclusion Criteria

• Self-reported pregnancy or breastfeeding.
• Patients on haemodialysis or peritoneal dialysis.
• Chronic liver disease with Child-Pugh score B or higher.
• Hypertension attributed to renal artery stenosis, primary hyperaldosteronism, pheochromocytoma, Cushing's syndrome, coarctation of aorta.
• History of any OSA surgical treatment to the palatal and hypopharyngeal regions, notably uvulopalatopharyngoplasty surgery (UPPP), palatal radio frequency ablation, tonsillectomy, lingual tonsillectomy, partial glossectomy, tongue base radio frequency ablation, genioglossal advancement, hyoid suspension, maxillomandibular advancement surgery (MMA) and active use of hypoglossal nerve stimulator.
• Patients with a good adherence to CPAP, defined as the use of CPAP for at least 4 hours/night on 70% of nights during the last 3 months.
• Pulmonary hypertension.
• Current diagnosed oncological disease.
• Patients with known chronic or acute infectious diseases.
• Other current severe progressive or uncontrolled disease which in the judgement of the investigator renders the patient unsuitable for the study

CONTROLS (individuals without hypertension with and without OSA) For each case, an age and gender-matched control will be selected.

• Pregnancy or breastfeeding.
• Patients on haemodialysis or peritoneal dialysis.
• Chronic liver disease with Child-Pugh score b or higher.
• History of any OSA surgical treatment to the palatal and hypopharyngeal regions, notably uvulopalatopharyngoplasty surgery (UPPP), palatal radio frequency ablation, tonsillectomy, lingual tonsillectomy, partial glossectomy, tongue base radio frequency ablation, genioglossal advancement, hyoid suspension, maxillomandibular advancement surgery (MMA) and active use of hypoglossal nerve stimulator.
• Patients with a good adherence to CPAP, defined as the use of CPAP for at least 4 hours/night on 70% of nights during the last 3 months.
• Pulmonary hypertension.
• Current diagnosed oncological disease.
• Patients with known chronic or acute infectious diseases.
• Patients with known chronic or acute infectious diseases.
• Other current severe progressive or uncontrolled disease which in the judgement of the investigator renders the patient unsuitable for the study.

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Centro Hospitalar Lisboa Ocidental

OTHER_GOV

Sponsor Role: collaborator

Centro Hospitalar de Lisboa Central

OTHER

Sponsor Role: collaborator

Hospital Beatriz Ângelo

OTHER

Sponsor Role: collaborator

Hospital Fernando Fonseca

UNKNOWN

Sponsor Role: collaborator

Hospital da Luz, Portugal

OTHER

Sponsor Role: collaborator

Universidade Nova de Lisboa

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maria E Monteiro, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidade NOVA Lisboa

Locations

Centro Hospitalar de Lisboa Central

Lisbon, , Portugal

Centro Hospitalar Lisboa Ocidental

Lisbon, , Portugal

Hospital Beatriz Ângelo

Lisbon, , Portugal

Hospital da Luz

Lisbon, , Portugal

Hospital Fernando Fonseca

Lisbon, , Portugal

Countries

Portugal

Other Identifiers

PTDC/MED-TOX30418/2017

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Kyntosa_02_20200428

Identifier Type: -

Identifier Source: org_study_id